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Ask the Doctor: 10 Questions About Progesterone Supplements

We asked Dr. Edward Marut, IVF Medical Director at Fertility Centers of Illinois, the 10 most common questions he hears about progesterone supplements:

What is progesterone?

Progesterone, a naturally occurring hormone in the body, is stored in fat tissue and produced by the corpus luteum, a hormone-secreting structure that develops from the follicle after an ovum (egg) has been released. Progesterone is found in the ovaries, adrenal glands and in the placenta during pregnancy. Each month, progesterone is released to stimulate the uterine lining in preparation for pregnancy. When progesterone levels are abnormal, menstrual periods can be irregular.

What role does progesterone play in fertility, conception and pregnancy?

Progesterone plays multiple roles in the reproductive cycle. In respect to fertility, progesterone is produced after ovulation. Sufficient amounts are needed to conceive and to maintain a pregnancy. If this production is inadequate, a progesterone supplement may be necessary. Once a woman conceives, progesterone plays a key role in thickening the uterine lining, which allows a growing embryo to attach to the womb. Prior to eight weeks of gestation, the production of progesterone is mainly derived from the corpus luteum. It is critical that progesterone levels support pregnancy during these early stages to prevent pregnancy loss. After ten weeks of gestation (even twelve in some women) progesterone is mainly derived from the trophoblasts, which play a key role in nourishing the embryo and forming the placenta.

What infertility issues does progesterone help to address?

Progesterone supplements are commonly used in women with infertility diagnoses such as ovulatory disorders, recurrent pregnancy loss, and in conjunction with Assisted Reproductive Technology (In Vitro Fertilization, Embryo Transfer, Frozen Embryo Transfer, etc.)  Progesterone supplements help to compensate for low production of the hormone after ovulation.

How do you determine if someone needs progesterone?

First, a patient’s medical history is assessed. The lack of regular menstrual cycles suggests a problem, such as with Polycystic Ovarian Syndrome. Previous pregnancy losses may be a sign of inadequate progesterone production. Properly timed blood tests to measure progesterone levels may be done in the woman who has regular menses. A biopsy of the uterine lining may even be done (although an uncommon practice these days) to determine a lack of progesterone effect. Sometimes, progesterone is used empirically, that is, just to make sure the level is normal, since you can’t have too much progesterone!

How is progesterone incorporated in an IVF cycle?

During the egg retrieval process, the cells that normally create progesterone after ovulation are removed along with the eggs. Progesterone supplements are then required to prepare the body for pregnancy and thicken the uterine lining to support successful embryo attachment in the womb. Progesterone may also be required during the pregnancy to safeguard against pregnancy loss. Continuation of progesterone supplementation is advisable, on an individual basis, even up to 12 weeks of pregnancy in a cycle where embryo transfer is done.

What are the side effects of progesterone?

Depending of the route of administration, there may be no side effects, especially with vaginal preparations, which have a direct uterine effect, rather than a systemic one. Vaginal discharge or irritation are possible with these forms.  If injectable or oral preparations are used, side effects may include pain, swelling and bruising at the injection site, headaches, breast tenderness, drowsiness, dizziness, fluid retention, bloating, hot flashes, constipation, and everything that mimics pregnancy symptoms! These symptoms may persist into a pregnancy as well, or stop when the drug is withdrawn.

Is progesterone safe for my baby and me?

Natural progesterone, which is used during fertility treatment, poses no threat to a mother and child. It is important to note that the Food and Drug Administration (FDA) does not differentiate between natural progesterone and synthetic progesterone (progestins) in its warnings. Progestins are mostly used to suppress ovulation and are found in birth control pills. They are only used in preparation for fertility treatment. In older studies synthetic progestins have been linked to a slightly increased risk of certain birth defects if used during pregnancy. The FDA has conducted a thorough review of relevant published studies and has found there is no increase in birth defects resulting from exposure to any progesterone in early pregnancy.

What different types of progesterone are prescribed?

During fertility treatment, a woman may be prescribed the following progesterone supplements in these common doses:

  • Crinone 8% (vaginal gel, once or twice per day)
  • Endometrin (vaginal tablets, 100mg 2-3x/day)
  • Progesterone in oil (intramuscular injection, 50-100 mg once a day)

These three routes noted above have been shown to be equally effective in fertility treatment. Less reliable are:

  • Prometrium (oral tablets, also prescribed for vaginal use, 200 mg 1-2x/day)
  • Progesterone suppositories (200 mg 1-2x/day, compounded by a pharmacy. Not FDA approved and unregulated)

The decision of what progesterone supplement will be used is dependent upon a physician’s judgment and personal preferences, as well as a patient’s particular situation.

In the past, intramuscular injections were commonly used as a result of the lack of other available preparations. Multiple studies have shown no difference in the outcome of IVF treatment when compared to vaginal progesterone, and some even have even shown superiority of vaginal progesterone.. An additional advantage of vaginal progesterone is that it does not cause the pain of intramuscular progesterone injections. In some circumstances, combinations of different types of progesterone may be prescribed.

What costs are associated with progesterone medication?

Compared to other fertility drugs, progesterone tends to be less expensive, and insurance generally covers one form or another.

Who is not a candidate for progesterone medication?

Patients who have had an allergic reaction to one form of progesterone should be switched to another form, even in the middle of treatment. Side effects specific to a certain form of progesterone are also a reason to switch.